molecular analysis of solid tumors

Conditions: Pediatric Solid Tumors

Summary: this study will prospectively characterize the molecular, cellular and genetic properties of primary and metastatic neuroblastoma, osteosarcoma, retinoblastoma, ewing sarcoma family of tumors, soft tissue sarcomas, adrenocortical tumors and liver malignancies. these cell isolates will be used for gene expression array analysis, genomic analysis by \[snp\] single nucleotide polymorphism chip, array \[cgh\] comparative genomic hybridization and next generation sequencing, and \[tem\] transmission electron microscopy analysis. additionally cell lines and orthotopic xenografts will be created from the obtained tumor specimens. the specificity of tcrs will be examined by comparing paired tcr from peripheral blood and tumor infiltrating cd4+ and cd8+ t cells. epigenetic studies will be performed looking at the methylation profile of these cells and to investigate the anti-tumor t cell response both pre- and post-pd1 inhibition.

each year approximately 2,200 children in the united states are diagnosed with neuroblastoma, osteosarcoma, ewing sarcoma family of tumors (esft), retinoblastoma, soft tissue sarcomas, adrenocortical tumors and liver malignancies. these aggressive pediatric solid tumors are developmental tumors that initiate during periods of tissue growth and morphogenesis in the neural crest, bone and soft tissues. the overall survival rate of these tumors in the advanced stage is less than 30%. despite intensive efforts over the past three decades using multiple therapeutic modalities including chemotherapy, surgery, radiation, autologous bone marrow transplant and biological agents there has been modest improvement in the long-term survival of these advanced stage pediatric solid tumors. a better understanding of the molecular, cellular and genetic changes that occur in the developing tissues as tumors form could improve the treatment of these devastating cancers. in particular, chemotherapeutic agents may be more effectively targeted to key regulatory enzymes or proteins if the study had a better understanding of the pathways that are disrupted as cells progress from preneoplastic lesions to metastatic disease. the specific aim of this proposal is to identify the changes in gene expression that occur in neuroblastoma, retinoblastoma, osteosarcoma, ewing sarcoma family of tumors \[esft\] and soft tissue sarcoma cells and to correlate these changes with genetic and cellular changes in the tumor cells. \[rna\] ribonucleic acid and genomic \[dna\] deoxyribonucleic acid will be isolated from neuroblastoma, retinoblastoma, osteosarcoma, esft \[ewing sarcoma family of tumors\] and soft tissue sarcomas (both primary and metastatic lesions) following surgery or bone marrow aspiration of previously untreated patients. additional testing will be conducted on tumor samples at any point during or following therapy in which a surgical specimen is obtained. when there is sufficient tumor sample remaining after pathological analysis and banking, fresh primary tumor cells will be used to prepare orthotopic xenografts and to establish models of each disease that recapitulate the advanced forms of neuroblastoma, osteosarcoma, ewing sarcoma family of tumors \[esft\], retinoblastoma and soft tissue sarcomas. for a small group of these excess samples, this study will perform fixation for electron microscopy and process the samples for \[tem\] transmission electron microscopy analysis. these studies will complement our active research program characterizing the molecular, cellular and genetic features of genetically engineered mouse models of each of these diseases. biological samples from the cohort of patients treated at st. jude children's research hospital will be complemented with samples collected and processed by collaborating institutions around the world. samples collected from international collaborators will be used for analysis of \[dna\] deoxyribonucleic acid and \[rna\] ribonucleic acid to complement the st. jude children's research hospital cohort. through this collaboration the study anticipates that they will be able to obtain enough fresh tumor samples to improve their understanding of multistage tumorigenesis in pediatric solid malignancies.

Eligibility criteria:
inclusion criteria: * must have a suspected or known diagnosis of neuroblastoma, osteosarcoma, ewing sarcoma family of tumor or soft tissue sarcoma based on the initial diagnostic workup and evidence of gross disease amenable to excision. specimens may be collected at some or all of the following time points: initial biopsy, bone marrow aspiration procedures, tumor resection, and at time of possible relapse. * patients with a diagnosis of retinoblastoma based on initial diagnostic workup and who require enucleation may be enrolled if there is no active therapeutic or biologic protocol for retinoblastoma. * the patient or his/her legal guardian, as appropriate, must provide written informed consent within 30 days of the removal of the first collection of tissue/bone marrow/blood sample for this protocol. * the patient is being seen at st. jude children's research hospital or at a collaborating institution. * patients must be less than or equal to 25 years old at the time of enrollment. exclusion criteria: * patient is known to be hepatitis b, hepatitis c and/or hiv positive.

Keywords: neuroblastoma retinoblastoma osteosarcoma rhabdomyosarcoma ewing sarcoma non-rhabdomyosarcoma soft tissue sarcoma adrenocortical tumors liver malignancies